Systems engineering N-glycans of recombinant therapeutic proteins

Protein N-glycosylation reactions form a distributed reaction network spanning over different compartments of Golgi apparatus. The resulting glycan structures are influenced by glycosylation enzymes, the supply rate of nucleotide sugars, as well as competition among extending glycan substrates for a common enzyme and among different enzymes for a common substrate. Controlling the glycan profile of a therapeutic protein product is important for product quality for both innovative drugs as well as biosimilars. Metabolic engineering of the glycosylation pathway offers a venue for modulating the glycan profile. We have taken a systems engineering approach to identify, through model assisted design, the genetic manipulations that may steer the glycan flux to the desired path. However, unlike the energy metabolism pathway for which a small number of enzymes play pivotal roles in controlling the flux, the glycosylation pathway lacks key regulated steps as easily identifiable targets for genetic alteration to re-direct the flux. The model prediction thus serves only as a imprecise guide rather than a clear beacon. Furthermore, very likely multiple genetic alterations are needed in order to steer glycan flux distribution. A scheme of rapid construction of gene combinations to facilitate genetic engineering of the cell is necessary. We establish a golden gate assembly workflow for production of multi-gene constructs for engineering the glycan biosynthesis pathway. Libraries containing promoters of varying strengths, terminators, and glycosylation related coding sequences of interest, all refactored to be devoid of type IIS restriction sites, were synthesized. In the first level of assembly, an additional library of single gene constructs were formed from these base components with single reactions. In the second level of assembly, these monocistrons were then combinatorically combined to form a multi-gene cassette library. In an application of this approach, the N-glycosylation pattern of a recombinant IgG produced in CHO cells was examined with a stoichiometric network visualization tool (GlycoVis) to track the reaction paths which lead to the product glycans and identify galactosylation as potentially limiting glycan maturation. Cassettes consisting of sequences coding for nucleotide sugar synthesis enzymes, nucleotide sugar transporters, and glycosyltransferases were then selected to engineer the IgG producing cell. Multiple cassettes successfully directed the glycosylation to produce antibody with desirable glycoforms. These results served to refine our model parameters and sharpen its predictive capabilities. This combination of systems analysis and synthetic glycoengineering can be broadly applied and enhances our capability to steer N-Glycan patterns and control the quality of therapeutic proteins

Visual communication design: a neglected factor in nutrition promotion via packaged food labels

Packaging design is a communication device and a critical component in branding strategy, and has relevance for food policy. Presently, packaging-related nutrition policy initiatives focus on the role of regulated claims, nutrition information panels and front-of-pack nutrition labels to help guide consumer food choices and address high prevalences of discretionary and ultra-processed food consumption in many countries. However, these nutrition labelling systems are not optimized as public health policy tools as many consumers do not use them to inform their food choices. Visual communication design theory posits that a designer orders the elements and principles of design into hierarchies that prioritize certain elements over others, and that some of these elements are more dominant and given more emphasis than others. The overall design of the package thereby directs consumer attention to some aspects of pack design (e.g., characters, contents of the package) and away from others (e.g., nutrition details). Dual processing frameworks propose that food decisions are made with the interplay between automatic and rational thinking processes. Packaging designs affect whether consumers rely predominantly on automatic or rational thinking to select a food. This narrative review outlines the role of food packaging design and how it impacts the clear communication of nutrition aspects of food products and how the use of nutrition information by consumers to make decisions may depend upon design structures in packaging. This article attests that nutrition scientists and policy makers should incorporate visual communication design into research on the food packaging as a public health promotion tool. A stronger focus on the communication of regulated front-of-pack nutrition information can be made with a re-evaluation of the hierarchy of elements in the front-of-pack design enabling consumers to make healthier decisions

The Future of Agriculture and Society in Iowa: Four Scenarios

Iowa is a leader in crop and livestock production, but its high productivity has had concomitant negative environmental and societal impacts and large requirements for fossil-fuel-derived inputs. Maintaining agricultural productivity, economic prosperity and environmental integrity will become ever more challenging as the global demand for agricultural products increases and the resources needed become increasingly limited. Here we present four scenarios for Iowa in 2100, based on combinations of differing goals for the economy and differing energy availability. In scenarios focused on high material throughput, environmental degradation and social unrest will increase. In scenarios with a focus on human and environmental welfare, environmental damage will be ameliorated and societal happiness will increase. Movement towards a society focused on human and environmental welfare will require changes in the goals of the economy, whereas no major changes will be needed to maintain focus on high throughput. When energy sources are readily available and inexpensive, the goals of the economy will be more easily met, whereas energy limitations will restrict the options available to agriculture and society. Our scenarios can be used as tools to inform people about choices that must be made to reach more desirable futures for Iowa and similar agricultural region

Making National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study

BackgroundExpert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community. ObjectiveUsing an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute–designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community. MethodsWe designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non–case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers’ practice. ResultsA total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians’ practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new. ConclusionsThrough an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians’ practices, significantly impact patient care in community practices, and be a source of new knowledge and education